Poster abstracts
Poster number 60 submitted by Kiel Tietz
Pnrc2 regulates 3’UTR-mediated decay of cyclic transcripts during somitogenesis
Kiel T. Tietz (Department of Molecular Genetics, The Ohio State University), Thomas L. Gallagher (Department of Molecular Genetics, The Ohio State University), Zachary T. Morrow (Department of Molecular Genetics, The Ohio State University), Nicolas L. Derr (Department of Molecular Genetics, The Ohio State University), Sharon L. Amacher (Department of Molecular Genetics, The Ohio State University)
Abstract:
Vertebrate segmentation is regulated by the segmentation clock, a biological oscillator that controls periodic formation of embryonic segments. This molecular oscillator generates cyclic gene expression in the tissue that generates somites and has the same periodicity as somite formation. Molecular components of the clock include the her/Hes family of transcriptional repressors, but additional transcripts also cycle. Maintenance of clock oscillation requires that transcriptional activation and repression, RNA turnover, translation, and protein degradation are rapid (one cycle is 30 minutes in the zebrafish). We previously isolated a zebrafish segmentation clock mutant, tortuga, that has elevated levels of cyclic transcripts. We show that loss of proline-rich nuclear receptor coactivator protein Pnrc2 is responsible for cyclic transcript accumulation in tortuga deletion mutants and that a new pnrc2 loss-of-function mutant displays an identical phenotype. pnrc2 mRNA is maternally provided and zygotically expressed, and in maternal-zygotic pnrc2 mutants, cyclic transcripts perdure even longer. We show that the her1 3’UTR confers instability to otherwise stable transcripts in a Pnrc2-dependent manner indicating that the 3’UTR of cyclic transcripts is critical for Pnrc2-mediated decay. Preliminary data suggests the last half of the 725 nucleotide (nt) her1 3’UTR is sufficient to convey rapid instability and we are currently examining features that reside in the last 363 nts of the 3’UTR that may confer Pnrc2-mediated decay. Interestingly, cyclic protein levels do not accumulate in pnrc2 mutants, suggesting that stabilized cyclic transcripts are not efficiently translated and that translation may be controlled by an additional post-transcriptional mechanism. Our work explores mechanisms regulating oscillation dynamics during somitogenesis and will further our understanding of pathways controlling post-transcriptional gene regulation.
Keywords: mRNA decay, her1, genetic oscillations